Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling

MAbs. May-Jun 2014;6(3):774-82. doi: 10.4161/mabs.28612. Epub 2014 Apr 2.

Abstract

Interleukin-6 (IL-6) is a critical regulator of the immune system and has been widely implicated in autoimmune disease. Here, we describe the discovery and characterization of olokizumab, a humanized antibody to IL-6. Data from structural biology, cell biology and primate pharmacology demonstrate the therapeutic potential of targeting IL-6 at "Site 3", blocking the interaction with the signaling co-receptor gp130.

Keywords: IL-6; antibody; gp130; interleukin 6; neutralization; olokizumab; site 3; structure.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal, Humanized / chemistry
  • Antibodies, Monoclonal, Humanized / genetics
  • Antibodies, Monoclonal, Humanized / immunology*
  • Antibodies, Neutralizing / chemistry
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology*
  • Antigen-Antibody Complex / chemistry
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / therapy
  • Binding Sites
  • Crystallography, X-Ray
  • Cytokine Receptor gp130 / antagonists & inhibitors*
  • Cytokine Receptor gp130 / chemistry
  • Cytokine Receptor gp130 / immunology*
  • Female
  • Humans
  • Hybridomas / immunology
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / genetics
  • Immunoglobulin Fab Fragments / immunology
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / chemistry
  • Interleukin-6 / immunology*
  • Macaca fascicularis
  • Models, Molecular
  • Molecular Sequence Data
  • Rats
  • Sequence Homology, Amino Acid

Substances

  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Antigen-Antibody Complex
  • IL6 protein, human
  • Immunoglobulin Fab Fragments
  • Interleukin-6
  • Cytokine Receptor gp130
  • olokizumab

Associated data

  • PDB/4CNI